Hassan, Shaimaa; (2023) Life during Dormancy: Genetic Regulation in Fission Yeast Spores and in Killifish Diapause. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Dormant stages allow organisms to survive in life-threatening environments for extended periods of time. Dormancy is characterised by a reversible arrest of cell replication and increased stress resistance. In addition, dormancy involves reprogramming of gene expression and energy metabolism from a mode of proliferation and development to a mode of suspended growth, possibly including suspended ageing. Here I study the spores of fission yeast and diapause embryos of turquoise killifish to reveal similarities in transcriptome and proteome changes during dormancy. Moreover, I uncover some conservation in the genetic regulation of dormancy and halted ageing across different organisms and dormant stages, including yeast quiescence and worm dauer stages. In particular, I find ribosomal proteins and autophagy play critical roles in supporting dormancy in yeast and killifish. Supporting this result, functional analysis using Barcode sequencing of the genome-wide deletion library for fission yeast identifies ribosomal proteins and autophagy as important factors for survival during dormancy. Furthermore, while traditionally it has been assumed that spores in yeast and diapause in killifish equate to suspension biological activity, I find that both dormant states can respond to environmental or physiological triggers by altering their gene-expression programmes. Specifically, this response includes proteomic and transcriptomic changes to heat stress as well as changes with the chronological passing of time following their formation. While some of these genetic changes mimic non-dormant yeast stress responses, they differ from expression signatures observed during ageing. This finding is consistent with the idea that dormant yeast and killifish cells are not ageing in the same manner as non- dormant cells, or that ageing is even suspended during dormancy. Finally, as dormant stages are a state of suspended activity, events occurring during the dormant stage are not thought to affect the organism in post-dormant cells. Intriguingly, I find that the stress experienced during dormancy and the duration the organism stays in dormancy is ‘remembered’ and can affect post-dormancy recovery in both yeast and killifish. This phenomenon is evidenced by changes in gene expression profiles. I also observe subtle differences in stress resistance and chronological lifespan in germinates from stressed or old spores. This is exhibited by a type of hormesis where sub-lethal stress during dormancy might confer a slight lifespan extension in the post-dormant state. These new insights transform our understanding of “dormant states” and the implication of dormancy to post-dormancy stress survival and ageing.

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